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  3. Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity

  • Nat Cell Biol. 2024 Aug;26(8):1346-1358. doi: 10.1038/s41556-024-01462-3.
Rong-Yi Shi # 1 2,  Neng Zhou # 1 3,  Li Xuan # 4,  Zhong-Hui Jiang # 4,  Jing Xia 1,  Jian-Min Zhu 1,  Kai-Ming Chen 1,  Guo-Li Zhou 5,  Guo-Pan Yu 4,  Jun Zhang 6,  Chuanxin Huang 7,  Ai-Bin Liang 8,  Kai-Wei Liang 9,  Hao Zhang 10,  Jian-Feng Chen 11,  Dachuan Zhang 12,  Yi Zhong 13,  Qi-Fa Liu 14,  Guo-Qiang Chen 15 16,  Cai-Wen Duan 17 18
Affiliations

Affiliations

  • 1 Key Laboratory of Pediatric Hematology and Oncology in National Health Commission, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
  • 2 School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China.
  • 3 Fujian Branch of Shanghai Children's Medical Center, SJTU-SM and Fujian Children's Hospital, Fujian, China.
  • 4 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 5 Shanghai Immune Therapy Institute, Renji Hospital, SJTU-SM, Shanghai, China.
  • 6 Department of Biology, College of Life Sciences, Shanghai Normal University, Shanghai, China.
  • 7 Shanghai Institute of Immunology and Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis, Chinese Ministry of Education, Faculty of Basic Medicine, SJTU-SM, Shanghai, China.
  • 8 Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
  • 9 Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
  • 10 Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, SJTU-SM, Shanghai, China.
  • 11 State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
  • 12 Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis, Chinese Ministry of Education, SJTU-SM, Shanghai, China.
  • 13 Shanghai Immune Therapy Institute, Renji Hospital, SJTU-SM, Shanghai, China. zhongyi@sjtu.edu.cn.
  • 14 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China. liuqifa628@163.com.
  • 15 School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China. chengq@shsmu.edu.cn.
  • 16 State Key Laboratory of Systems Medicine for Cancer and Research Unit 2019RU043, Chinese Academy of Medical Sciences, Renji Hospital, SJTU-SM, Shanghai, China. chengq@shsmu.edu.cn.
  • 17 Key Laboratory of Pediatric Hematology and Oncology in National Health Commission, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China. caiwenduan@sjtu.edu.cn.
  • 18 Fujian Branch of Shanghai Children's Medical Center, SJTU-SM and Fujian Children's Hospital, Fujian, China. caiwenduan@sjtu.edu.cn.
  • # Contributed equally.
PMID: 39039181 DOI: 10.1038/s41556-024-01462-3
Abstract

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44-CD62L- T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating Integrin β7 and downregulating C-X-C motif Chemokine Receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through Integrin α4-vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif Chemokine Receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine-BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.

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